1. Mutations

2. The picture shows a human genome Karyotype. Look at it carefully and discuss.

3. What I need to know:- 1.That genetic disorders are caused by changes to genes or chromosome 2.This results in proteins not being expressed or the protein expressed not functioning correctly 3.Mutations are rare and can be artificially increased by mutagenic agents 4.Single gene mutations is the alteration of a DNA nucleotide (insertion, deletion and substitution) 5.Single nucleotide substitutions can be missense, nonsense or splice site. 6.Chromosomes can be altered by deletion, duplication or translocation.

4. A mutation is a change in the structure or amount of genetic material in an organism. It can vary from tiny changes in DNA structure of gene level to large scale alterations in chromosome structure or number. When such a change in genotype produces a change in phenotype the individual affected is a called a MUTANT

5. Frequency of Mutation Naturally occurring mutations are very rare. They occur spontaneously and randomly. Most are recessive so don’t show in the phenotype for several generations. For it to show in the first generation it must be dominant or sex linked.

6. A mutation rate is worked out as the number of mutations at the gene locus per million This can vary from gene to gene and species to species

7. Mutagenic Agents Usually chemical which ARTIFICIALLY increase the chances of bringing about a mutation Eg, Chemicals ( mustard gas, lead oxide) Radiation ( gamma rays, x-rays, UV lights)

8. Genetic Disorder A condition or disease that can be shown to be directly related to a individual’s genotype is called a genetic disorder. A change in the gene caused by a mutation will result in either no protein being made or a faulty protein being expressed. Some mutations may be harmful (lethal) as essential proteins (in metabolic pathways for example) are not being processed properly.

9. Gene mutations Single gene mutation – involves an alteration of a nucleotide sequence in the gene’s DNA Point mutations – involves a change in one nucleotide in the DNA sequence of a single gene. Types of point mutations include substitution; insertion and deletion

10. Substitution – only one amino acid changed G U A Valine DNA mRNA Amino acid C T T G A A Glutamic acid Normal C A T Mutant

11. Insertion – all amino acids altered (frameshift) A G A G T C DNA mRNA Amino acid Normal U C U C A G Serine Glutamine Proline A G A G G T C Mutant U C U C C A G Serine

12. Deletion – all amino acids altered (frameshift) A G A G C T Mutant U C U C A G A DNA mRNA Amino acid Normal A G A G T C T Serine Glutamine U C U C G A SerineAlanine

13. Splice-site mutations Remember: - before mRNA leaves the nucleus it is spliced Splicing is controlled by specific nucleotide sequences at splice sites on the introns If a mutation occurs at one of these splice sites, the codon may be affected and the intron will remain attached to the mRNA

14. A gene mutation can also be the result of a trinucleotide repeat expansion This can result in the production of a defective protein possessing a string of extra copies of a particular amino acid which may silence the gene and it fails to express any protein

15. Impact on protein structure Missense Following a substitution, the altered codon codes for an amino acid that still makes sense but not the original sense Nonsense As a result of a substitution, a codon that used to code for an amino acids is exchanged for one that acts as a stop codon. It causes protein synthesis to be halted prematurely and results in the formation of a polypeptide chain that is shorter than normal and unable to function.

16. Chromosome structure mutations Chromosome mutations are normally large changes which are usually detectable under the microscope during cell division. They usually occur during crossing over when the number or sequence of genes may be altered. When a chromosome is broken it has a sticky end which can join onto other chromosomes. As the change can be substantial the mutation is harmful There are several ways this can happen:

17. Chromosome mutations Type of Mutation DescriptionSignificance DeletionGenes chopped outGenes lost DuplicationGenes copied twiceDuplicated gene could mutate TranslocationGenes stick to different chromosomes Problems of homologous pairing.

18. Deletion 1237812378 New chromosome 1234567812345678 BREAK Original chromosome 456456 Deleted genes

19. Duplication 1234567812345678 BREAK Original chromosome New chromosome 1234345567812343455678 Duplicated Genes from Homologous chromosome

20. Translocation 23 24 1 2 3 4 5 21 22 Translocated genes 1234512345 21 22 23 24 Chromosome A Chromosome B BREAK

21. Case studies There are many genetic disorders that arise from single gene and chromosome mutations.

22. Glossary CHROMOSOMAL MUTATION - a type of mutation involving alteration(s) in chromosome structure. Examples include deletion, duplication and translocation. DELETION MUTATION - a gene mutation in which a base or part of a chromosome is removed. INSERTION MUTATION – a gene mutation in which one or more bases are added to a gene sequence. MISSENSE - A form of point mutation resulting in a codon that codes for a different amino acid than originally planned for.

23. MUTAGENIC AGENT – a factor which causes mutations to occur, e.g. a chemical or certain forms of radiation. MUTATION – an unplanned, random change to the genetic code which can be harmful. NONSENSE - A form of point mutation resulting in a nonsense codon that does not code for an amino acid and leads to a protein product that is cut short. SPLICE SITE MUTATION - a gene mutation that results in an intron being retained by modified mRNA which could result in an altered protein which may not function properly. SUBSTITUTION MUTATION – a gene mutation in which one base is substituted by another.